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The UN Assistance Mission in Afghanistan said it "expresses its grave concern" over the deaths.
Eighteen of the civilians, "nearly all women and children," were killed in Helmand's Sangin District amid airstrikes targeting "anti-government elements," UNAMA said.
The NATO-led Resolute Support Mission has begun an investigation into the incident, UNAMA said.
NATO bills the mission as an effort "to train, advise and assist the Afghan security forces and institutions." It consists of more than 13,000 troops, more than half of which come from the United States.
Helmand, in southern Afghanistan, had 891 civilian deaths or injuries last year, the highest total in the country outside of Kabul, UNAMA said.
UNAMA also cited Saturday's Taliban suicide car bombing in Lashkar Gah, capital of Helmand province, that killed at least eight people and injured at least 19 others. Many of the casualties were child vendors.